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Platelet-derived growth factor BB enhances osteoclast formation and osteoclast precursor cell chemotaxis

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Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Enhanced osteoclast formation increases bone resorption, which triggers bone remodeling. Platelet-derived growth factor BB (PDGF-BB) enhances precursor cell homing, angiogenesis, and bone healing, and thereby could also treat osteoporosis. However, the effect of PDGF-BB on osteoclast formation is not fully understood. We investigated whether exogenous recombinant PDGF-BB directly affects osteoclast formation and osteoclast precursor cell chemotaxis. The murine monocyte–macrophage cell line RAW264.7 and bone-marrow-derived macrophages were cultured with recombinant mouse PDGF-BB with or without a platelet-derived growth factor receptor β inhibitor (AG-1295) or a Janus kinase 2 inhibitor (AG-490) to analyze the effect on osteoclastogenesis in vitro. PDGF-BB with or without AG-490 or AG-1295 was locally administrated in the mandibular fracture of 16-week-old Sprague Dawley rats (n = 18) for 1–2 weeks to analyze the effect on osteoclastogenesis in vivo. The effect of the treatments on osteoclast formation, osteoclast precursor cell migration, and expression of osteoclastogenic signaling molecules was analyzed. PDGF-BB enhanced osteoclast formation both in vitro and in vivo, but AG-490 and AG-1295 inhibited this effect. PDGF-BB enhanced phosphorylation of extracellular-signal-regulated kinase 1/2 (ERK1/2), Akt, and signal transducer and activator of transcription 3 (STAT3) in RAW264.7 cells. AG-490 inhibited PDGF-BB-induced STAT3 phosphorylation. PDGF-BB enhanced RAW264.7 cell migration and gene expression of osteoclastogenic signaling molecules (i.e., nuclear factor of activated T cells 1, dendrocyte-expressed seven transmembrane protein, and B-cell lymphoma 2), and treatment with AG-1295, AG-490, or S3I-201 (a STAT3 inhibitor) reduced this effect. PDGF-BB enhanced osteoclast formation, osteoclast precursor cell chemotaxis, and phosphorylation of STAT3, Akt, and ERK1/2. but AG-1295 and AG-490 reduced this effect. These findings reflect the complexity of PDGF-BB in bone biology.

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Acknowledgment

This work was supported by the National Natural Science Foundation of China (no. 81271107, no. 81470718, and no. 81100736).

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    Authors and Affiliations

    1. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan, 430079, People’s Republic of China

      Dian-qi Li, Qi-long Wan & Zu-bing Li

    2. Department of Oral and Maxillofacial Trauma and Plastic Surgery, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan, 430079, People’s Republic of China

      Dian-qi Li, Qi-long Wan & Zu-bing Li

    3. Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, People’s Republic of China

      Janak L. Pathak

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    1. Dian-qi Li
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    Correspondence to Zu-bing Li.

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    D. Li and Q. Wan contributed equally to this work.

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    Li, Dq., Wan, Ql., Pathak, J.L. et al. Platelet-derived growth factor BB enhances osteoclast formation and osteoclast precursor cell chemotaxis. J Bone Miner Metab 35, 355–365 (2017). https://doi.org/10.1007/s00774-016-0773-8

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    • DOI: https://doi.org/10.1007/s00774-016-0773-8

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